Spillover: Animal Infections and the Next Human Pandemic

Quammen takes the reader through medical history to examine the long struggle to understand what viruses were. Into the 20th century, experts treated viruses like yellow fever without knowing their cause. Even today, experts debate whether viruses are alive. The discovery of viruses was partly made possible by the development of microscopes, since this led to the “germ theory” of disease—that ailments were caused by tiny organisms. The germ theory’s discoveries, however, were limited to bacteria because they could be seen via available equipment and grown in laboratories.

In the 1890s, a Russian scientist studying disease in tobacco plants discovered that sap put through a filter remained infectious. This “filterable” nature of viruses was their first identified property. Another researcher discovered that dilution did not make the sap less infectious when the diluted sap was applied to a second host—indicating it needed a host to thrive. Eventually filtration techniques were applied to prove that “foot and mouth” disease in cattle was also a virus, and yellow fever, still unseen, was proven to be a virus transmitted by mosquitoes (265). Scientists began using the term “filterable virus” to describe the unseen agents, and the doctor and medical historian Hans Zinsser posited that viruses, like bacteria, could pass between humans and animals.

The difficulty of growing viruses in a laboratory is an important feature to understanding them—they are “obligate intracellular parasites” that need to reside in other living hosts (267). Viruses have four basic tasks to accomplish:

how to get from one host to another, how to penetrate a cell within that host, how to commandeer the cell’s equipment and resources for producing multiple copies of itself, and how to get back out—out of the cell, out of the host, on to the next (268).

Viruses have a particular structure that allows them to accomplish this objective. One aspect of this structure is a wrapping for the protein that makes up the viral genetic code, the capsid, which “protects the viral innards when they need protection and it helps the virus lever its way into cells” (268). Each individual particle, or virion, has “spikes” outside it that determine which kinds of cell it can access. Because viruses do not have cell walls or other parts similar to a bacterium, they are invulnerable to antibiotics. 

Viral genetic code can consist of either RNA or DNA. DNA mutates less frequently than RNA does. Quammen highlights this distinction when he declares, “RNA viruses therefore evolve quicker than perhaps any other class of organism on Earth. It’s what makes them so volatile, unpredictable, and pesky” (271). Though we think of viruses as deadly, sometimes they reach “equilibrium” with their hosts, which is “disrupted” in every instance of spillover into humans.

Next, Quammen turns to one virus in particular, herpes B, commonly found in macaques. In 1932, a viral researcher at NYU named William Brebner was working with the monkeys to develop a polio vaccine and was bitten by a subject. He developed a fever, liver issues, and respiratory problems. He died a few weeks after his initial encounter with the chimp, and an autopsy and later testing by his colleagues found that rabbits developed similar symptoms when injected with samples from his body. A filtered essence was extracted from the rabbits and named the “B virus” after Brebner.

Herpes B kills about half of infected people. Cases rose sharply during the years scientists worked on a polio vaccine, then fell again. As recently as 1997, a lab technician died after being misdiagnosed. In the UK, infected macaques were exterminated at safari parks by the hundreds after a law was passed mandating euthanasia or containment for infected animals.

These incidents gave rise to debates in the scientific community about the necessary precautions to safely work with Herpes B. In the wild, macaques frequently live close to humans, especially as their habitats have been encroached upon, and no infections have occurred. In South Asia they are very common at Hindu and Buddhist temples, as both religions venerate and respect monkeys.

This practice led anthropologist Lisa Jones-Engel, an anthropologist, and her doctor husband Gregory Engel, to study herpes B exposure at a temple in Bali located in the Sangeh monkey forest. The monkeys there largely depend on food from tourists, and Bali is densely populated, leading to routine contact between people and the monkeys. The research team at Sangeh tested the monkeys and found all of the adults were infected with herpes B. No cases of human infection were found.

Quammen reports on his own visit to Bali and meeting with Engel and Jones-Engel. They worked in a Bangladeshi city called Sylhet, also home to a shrine with a large monkey population. The shrine at Chashnipeer Majar was an ideal location for trapping macaques, tranquilizing them, and then drawing their blood. After their monkey trapping, Lisa Jones Engel and Quammen talked about similarities between herpes B and Ebola, especially in terms of human response. In both cases, the disease makes people anxious, perhaps even hysterical, but person-to-person transmission is limited. Jones-Engel was against wholesale extermination of macaques found to have herpes B antibodies, since this is not the same as active infection, and because no evidence of human infection in Bali or elsewhere has emerged. Only 43 people have ever been infected with herpes B from a monkey.

Engel and Jones-Engel were also studying their primates for a disease called Simian Foamy Virus. There are numerous viruses in this family, perhaps “one per species of simian” in primates (287). Most of the monkeys at Sangeh had both herpes B and SFV. At least one cross-species infection had occurred and there might be others—what Jones-Engel called “The Next Big One” (289).

Quammen notes that he has referred to the “Next Big One” earlier in his work, as many scientists are concerned with it, and AIDS, the most recent “big one,” is still a major public health problem (289). Past incidents include polio, influenza in 1918-1919, smallpox in North America among indigenous people, and the Black Death. All of them illustrate how quickly diseases can spread in dense populations. It seems likely that the Next Big One, like its predecessors, will be viral.

To understand how these large disease events occur, Quammen relies on two key concepts. The first, “transmissibility,” is how easily a virus can spread from one host to another and remain there (290). Flu and SARS are easily transmitted in the air, which is why the 2003 SARS outbreak was so concerning to experts. Others, like West Nile, depend on mosquitoes to act as a “vector” by infecting host bloodstreams (292).

There are two kinds of transmission, which Quammen uses Ebola to illustrate. In the case of “ordinary” transmission, the disease moves from one animal to another in its (still unidentified) host population. In contrast, “extraordinary” transmission categorizes the events people recognize: blood from human Ebola victims infecting other people. However, this is “extraordinary” because so far it has not led to long-term survival for the virus.

The second concept, virulence, is the “measurable degree of a virus” (295). Some viruses exist in relative harmony with their hosts, but that does not mean that harmony is a natural or ideal state—HIV kills virtually all of its hosts without treatment, after all. The key question is one of “timing”—a virus should not kill its host before it has had time to reproduce and spread (296). In some cases, virulence can drop, as in one historical incident from Australia, the myxoma virus in rabbits. A white settler named Thomas Austin was enthusiastic about importing animals to the new continent, and his original 26 rabbits, which arrived in 1859, had resulted in a population of 600 million by 1950. The government decided to introduce myxoma virus on the theory that it would be more infectious in European rabbits than in Brazilian ones, as it was native to Brazil and merely caused skin irritations. The virus initially killed over 99% of rabbits but became less virulent over time.

This was less a case of mutual tolerance than of evolution keeping the virus potent. A biologist named Frank Fenner found five strains of myxoma, and the third, which still killed 70% of infected animals, was the most common. Fenner found that this strain produced a higher number of “infected lesions” while leaving the rabbits alive long enough to spread the contagion (301).

Quammen notes that these viral “strategies” come from millions of years of evolution (302). To explain more about this, he turns to another pair of scientists interested in applying mathematics to disease ecology, Robert May and Roy Anderson. They improved on the work of their predecessors by considering the impact of population size—the mortality rates caused by a disease as well as the other effects an outbreak has on a population, such as declining birthrates. When they applied their equation to myxoma, they found that it matched the data—an intermediate strain would come to surpass the others.

To conclude his understanding of emerging diseases and evolution, Quammen met with biologist Edward C. Holmes at Pennsylvania State University. Holmes turned his attention to RNA viruses and why so many of them are zoonotic. There are two reasons RNA viruses are significant, Holmes explained: “It’s not just the high mutation rates but also the fact that their population sizes are huge” (308). DNA viruses are more stable and rely instead on “stealth,” as chicken pox does when it comes back in adults as shingles. RNA viruses, by contrast, rely on their large numbers, since having a larger genome would result in so many errors the virus wouldn’t be able to sustain itself. Holmes explained another key compensation mechanism, saying, “they jump species a lot” (310).